Lymphoid tissue is the major reservoir and site of replication of the human immunodeficiency virus (HIV). We have previously demonstrated that HIV virions are trapped extracellularly in the processes of the follicular dendritic cells (FDC) of the lymphoid tissue germinal centers. This trapping serves as a source of infectious virus to the CD4+ T cells that migrate into the germinal centers to provide T-cell help in the induction of an HIV-specific immune response. Over time with HIV disease, the FDC network is destroyed and the lymph node architecture is disrupted. The mechanisms involved in the dissolution of the FDC network are unclear at present since infection of these cells with HIV is inefficient. The present study was aimed at characterizing the nature of the FDC as well as to establish cell lines for study of mechanisms of virus trapping and transfer of infection to CD4+ T cells. Our studies have demonstrated that human FDCs are bone marrow-derived and share a common precursor with B lymphocytes. We also created an Epstein-Barr virus (EBV) transformed FDC-like cell line which can induce HIV expression in latently infected cell lines and bind to complement and antibody coated HIV particles through complement receptors similar to primary FDCs. These results will allow us to identify the FDC precursor cells and further to delineate the mechanisms responsible for the destruction of lymphoid tissue, CD4 T-cell killing, and viral expression and propagation in HIV-infected individuals.